NM_001101669.3:c.1073-4025A>G

Variant names:

• chr4-142197220-T-C
• rs2627821
• NM_001101669.3:c.1073-4025A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001101669.3(INPP4B):​c.1073-4025A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 151,632 control chromosomes in the GnomAD database, including 58,979 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.88 (58979 hom., cov: 28)
• Consequence: INPP4B NM_001101669.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340

Genes affected

INPP4B (HGNC:6075): (inositol polyphosphate-4-phosphatase type II B) INPP4B encodes the inositol polyphosphate 4-phosphatase type II, one of the enzymes involved in phosphatidylinositol signaling pathways. This enzyme removes the phosphate group at position 4 of the inositol ring from inositol 3,4-bisphosphate. There is limited data to suggest that the human type II enzyme is subject to alternative splicing, as has been established for the type I enzyme. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP4B	NM_001101669.3	c.1073-4025A>G		intron_variant	Intron 14 of 25	ENST00000262992.9	NP_001095139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP4B	ENST00000262992.9	c.1073-4025A>G		intron_variant	Intron 14 of 25	5	NM_001101669.3	ENSP00000262992.4

Frequencies

GnomAD3 genomes AF: 0.876 AC: 132735 AN: 151514 Hom.: 58938 Cov.: 28

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.936

Gnomad FIN AF: 0.954

Gnomad MID AF: 0.817

Gnomad NFE AF: 0.946

Gnomad OTH AF: 0.896

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.876 AC: 132828 AN: 151632 Hom.: 58979 Cov.: 28 AF XY: 0.878 AC XY: 65037 AN XY: 74056

Gnomad4 AFR AF: 0.715

Gnomad4 AMR AF: 0.903

Gnomad4 ASJ AF: 0.834

Gnomad4 EAS AF: 0.957

Gnomad4 SAS AF: 0.937

Gnomad4 FIN AF: 0.954

Gnomad4 NFE AF: 0.946

Gnomad4 OTH AF: 0.897

Alfa AF: 0.875 Hom.: 8539

Bravo AF: 0.863

Asia WGS AF: 0.930 AC: 3235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.2
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2627821; hg19: chr4-143118373;